1. Technical Field of the Invention
The present invention relates to, as novel and useful industrial products, a novel class of 3-phenylpropanoic acid compounds that activate the Peroxisome Proliferator-Activated Receptor type receptors of subtype γ (PPARγ). This invention also relates to the process for preparing such compounds and formulation into pharmaceutical compositions for administration in human or veterinary medicine, or alternatively in cosmetic compositions.
2. Description of Background and/or Related and/or Prior Art
The activity of receptors of PPAR type has been the subject of numerous studies. See, as a guide, the publication entitled “Differential Expression of Peroxisome Proliferator-Activated Receptor Subtypes During the Differentiation of Human Keratinocytes”, Michel Rivier et al., J. Invest. Dermatol. 111, 1998, pp. 1116-1121, in which is listed a large number of bibliographic references relating to PPAR type receptors. Also see, as a guide, the file entitled “The PPARs: From orphan receptors to Drug Discovery”, Timothy M. Willson, Peter J. Brown, Daniel D. Sternbach, and Brad R. Henke, J. Med. Chem., 2000, Vol. 43, pp. 527-550.
The PPAR receptors activate transcription by binding to DNA sequence elements known as the peroxisome proliferator response elements (PPRE), in the form of a heterodimer with the retinoid X receptors (known as RXRs).
Three subtypes of human PPAR have been identified and described: PPARα, PPARγ and PPARδ (or NUC1).
PPARα is mainly expressed in the liver, whereas PPARδ is ubiquitous.
Of the three subtypes, PPARγ is the one that has been the most extensively studied. All the references suggest a critical role of PPARγ in the regulation of differentiation of adipocytes, where it is strongly expressed. It also plays a key role in systemic lipid homeostasis.
It has especially been described in WO 96/33724 that PPARγ-selective compounds, such as a prostaglandin-J2 or -D2, are potential active agents for the treatment of obesity and diabetes.
Moreover, the Assignee hereof has already described in WO 02/12210, WO 03/055 867 and WO 2007/049 158 the formulation of biaromatic compounds that activate PPARγ type receptors into pharmaceutical compositions, such compositions being useful for treating skin disorders associated with an anomaly of epidermal cell differentiation.
It nevertheless remains necessary to develop novel such compounds that have good activity and advantageous pharmaceutical properties.